Research Resources Much of this research is based on three large epidemiologic observational cohorts the AGES-RS (Age Gene/Environment Susceptibility-Reykjavik Study), and the HAAS (Honolulu Asia Aging Study), the Coronary Artery Risk Development in Young Adults Study (CARDIA). AGES-RS includes men and women born 1907-1935 and the HAAS includes Japanese American men born 1900-1919. Both AGES-RS and HAAS cohorts were established in the mid-1960s to answer questions about the heart disease epidemic that became a public health priority during that decade. CARDIA began in 1985-6 with a group of 5115 black and white men and women aged 18-30 years. The MRI sub-study in CARDIA fills the gap in the other cohorts by providing the opportunity to study prospectively changes in brain structure and function that occur during middle age. All studies have similar measures of cardiovascular risk factors in middle-age, which is invaluable when trying to understand epidemiologic studies designed to investigate etiology. Since the mid-life data are similar, and both studies identify dementia cases, this provides an excellent opportunity to replicate findings from one cohort, in the other cohort. The studies also have complementary measures of brain aging; whereas the HAAS includes a rich autopsy sub-study, AGES-RS has a wealth of cognitive, MRI and clinical data, while CARDIA has state-of-the-art measures on brain MRI. Based on this suite of studies we will gain a better understanding of what, when, who, and why certain groups should be targeted in the prevention and early management of CVD before irreversible damage and functional consequences occurs. They will also provide data on early MRI markers that may predict later age cognitive disorders. In order to increase the power of our studies, we are participating in the NINDS funded initiative, MARK_VCID, designed to identify blood and imaging based biomarkers of cerebro-vascular disease, and which can be used in trials to test new interventions. Findings Cardiovascular disease is an important and major component of the dementia that afflicts older age people. We have found that even in a middle age cohort, total brain volume, white matter lesion load, white matter tissue integrity and cerebral blood flow are associated with one or more cardiovascular risk factors, including elevated blood pressure, diabetes, smoking, and sedentary behavior, and that these risk factors lead to measurably lower scores on cognitive function tests. Control of one single cardiovascular risk factor, mid-life hypertension, could significantly reduce the 25% of the burden of ADRD. The data also suggest that without more research on this vascular aspect of dementia, meaningful interventions will not be identified and a portion of the dementia epidemic not addressed.